Treatment Stratification According to Early Response to Mega-CHOP, Based on CT and Gallium ⁶⁷ Scan (G⁶⁷S) with or without IFE Salvage Therapy Followed by Peripheral Autologous Stem Cell Transplant (PBSCT) in Patient with Poor Prognosis Aggressive Lymphoma. A Preliminary Report from a Prospective GEL/TAMO Trial.

Background. Patients with IPI 2,3 large cell lymphoma have a poor outcome with long term survival lower than 50%. Evaluation of response only with CT scan shows often residual masses which can be tumoral or fibrotic. Gallium ⁶⁷S discriminate better these two situations and therefore can help to decide further strategies.

Aim. To assess the efficacy of PBSCT in patients with poor prognosis aggressive NHL according to previous early response to Mega-CHOP evaluated with CT & Ga⁶⁷S

Patients & methods. Inclusion criteria were: G⁶⁷S positive large cell B cell lymphoma with IPI score ≥ 2 or IPI <2 with high β2 microglobulin or peripheral T cell lymphoma (PTCL), except ALK+ anaplastic lymphoma regardless of IPI. Patients were evaluated after 3 cycles of Mega-CHOP. Those in CR (CT scan, Ga⁶⁷S negative) or uCR (CT scan positive, Ga⁶⁷S negative) received a 4rd Mega-CHOP followed by BEAM and PBSCT. Those with positive Ga⁶⁷S received IFE or ESHAP (x2) regimens followed by BEAM and PBSCT. Patients with refractory disease (RD) were dropped from the study. Since 2001, 112 patients have been registered and 87 have finished the treatment. Median age was 52 years (20–67 years) and 49% were males. Seventy one (72%) had a DBLCL, 8 (7%) a grade 3 FL and, 24 (21%) PTCL. Sixty two (88%) had IPI ≥ 2, and 12% IPI 1. Doses were for Mega- CHOP: Cy 1,5 g/m2, ADR 65 mg /m2 and VCR 2 mg on day 1 and Pred 60 mg /m2 days 1 – 5) on a 21 day schedule and for IFE: Ifosfamide 10 gr/m2 and VP16 900 mg/m2 (days 1– 3) with Mesna.

Results: After 3 Mega-CHOP, 47 patients (42%) were considered on CR or uCR due to a negative Ga⁶⁷S, 48(43%) were on PR and 16 (14%) were refractory. Two patients were early deaths. After IFE 18/46 (39%) achieved CR, 19 (41%) PR and 9 (20%) progressed. Overall, 87 patients received PBSCT and are valuable for response. Twenty nine patients (26%) died, 20% due to lymphoma and 6% due to toxicity. With 24 months of median follow-up (8 to 51 months), 81 patients are alive, 67 (60%), disease free. Overall Survival for Ga⁶⁷S negative patients after 3 Mega-CHOP was 69 % vs. 67% for Ga⁶⁷S positive (p=0,14) and Event free survival 68% vs. 61% (p=0,84). In the univariate analysis, the only significant variable associated with outcome was non CR or PR after MEGACHOP ± IFE vs. RD (p=0,007).

Conclusion: Our preliminary results suggest that early salvage therapy can overcome the poor outcome of patients with bad prognosis aggressive lymphoma. Moreover, this early evaluation could identify patients with poor prognosis who only need a short treatment (4 Mega-CHOP+PBSCT).